1. Field of the Invention
This invention relates to a use or method of preventing and/or treating diseases in subjects by administering a fermented soy extract, FSE, to the subjects in need of the prevention and/or treatment of the diseases. The fermented soy extract is particularly useful in preventing and/or treating cancer, preventing infections, reducing the incidence of infections, treating infections, preventing and/or treating asthma, preventing and/or treating inflammation, e.g. inflammation of the skin, modulating the immune system and treating immune disorders. The present invention also relates to methods for selectively killing tumor cells by inducing cell apoptosis, reducing cell proliferation and angiogenesis of tumor cells, and methods of inhibiting lipoxygenase, e.g. LOX-5, LOX-12 and/or LOX-15. The fermented soy extract is also useful in improving the health of subjects in need of the improvement and in promoting the health of pregnant women or infants.
2. Description of the Prior Art
Cancer chemoprevention is the use of natural or pharmaceutical agents to prevent, slow or halt the process of carcinogenesis. These agents inhibit the development of invasive cancer either by blocking the DNA damage that initiates carcinogenesis or by diverting the progression to a benign outcome, such as apoptosis or differentiation of these precancerous cells. Chemopreventive agents could be defined as: substances that reduce the synthesis of carcinogens in the body; Chemicals that enhance their detoxification by Phase I or Phase II enzymes; antioxidants that scavenge free radicals; and chemicals that trap ultimate carcinogens preventing their interaction with DNA. It is of paramount importance to ensure that chemopreventive agents must be nontoxic and relatively free of side effects, because they have to be administered over a long period of time in order to establish whether they possess efficacy in humans. For many candidate agents, mechanisms of action can be well characterized using human or other mammalian cells propagated in vitro, whereas potential toxic effects can often be predicted by administration to animals in in vivo studies. Furthermore, these agents should be taken orally, in forms of pills, foods, or beverages modified to increase the convenience and obedience of daily consumption.
Dietary epidemiological studies of cancer development have generated new clues about micronutrients and other dietary components to act as efficacious cancer preventive agents. For example, intake of soybeans and soy-based products is associated with a lower risk of several types of cancers including breast, prostate and colon cancer. Experiments in various animal models also suggested that soy consumption could decrease tumor number, incidence, latency, multiplicity and metastasis. Soybeans are the most concentrated source of isoflavones in the human diet. They also contain many other compounds including saponins, phytosterols, soy phytates, protease inhibitors, phenolic acids, complex sugars, boron, lecithin, omega-3 fatty acids and folic acid, these compounds may impart health benefits. In general soybean-related products containing higher amount of aglycones than glucoside conjugates of isoflavones would be preferable for cancer prevention. It has been demonstrated that microbial fermentation might influence the isoflavones content and isomer distribution of soybeans and further alter the availability and metabolism in human. Glycoside conjugates may be converted to aglycones by microbes during fermentation, which also results in increasing in soluble nitrogen compounds, riboflavin, niacin, pantothenic acid, biotin, folic acids and nicotinic acid. These aglycones of isoflavones, such as genistein and daidzein, can influence steroid metabolism, inhibit protein tyrosine kinase activity, inhibit topoisomerase activity, reduce angiogenesis in vitro and in vivo, inhibit malignant cell proliferation, induce cell differentiation and stimulate apoptosis.
Apoptosis, characterized by cell shrinkage, membrane blebbing, nuclear pyknosis, chromatin condensation and genomic fragmentation, is a strictly regulated process responsible for the ordered removal of superfluous, aged and damaged cells. It does not only play an important role in the development and maintenance of tissue homeostasis but also represents an effective mechanism by which harmful cells can be eliminated. Since apoptotic programs can be manipulated to produce massive changes in cell death, the genes and proteins controlling apoptosis are potential drug target. In fact, most anticancer drugs induce apoptosis directly, thus providing less opportunity for acquired drug resistance, decreasing mutagenesis and reducing toxicity. In addition, induction of apoptosis can also serve as an excellent surrogate end-point biomarker in chemoprevention.
Many data point out that intracellular oxidative metabolites play a significant role in the regulation of apoptosis. For instance, some apoptosis-inducing agents are either oxidants or stimulators of cellular oxidative metabolisms, whereas many inhibitors of apoptosis show antioxidant activities. Indeed, factors for oxidative stress such as ROS production, lipid peroxidation, down-regulation of antioxidant defenses characterized by reduced glutathione (GSH) levels, and progressive decline in the transcript levels of superoxide dismutase (SOD), catalase and thioredoxin have been observed in some apoptotic processes. Moreover, ROS can also play an important role in apoptosis by regulating the activity of certain enzymes involved in the cell death pathway.
The association of neutropenia and infection in patients with neoplastic disorders who are receiving myelosuppressive chemotherapy was established more than three decades ago. Infection continues to be a leading cause of morbidity and mortality in such patients. The risk of infection is further enhanced by the toxicities of the cytotoxic drugs to the mucous membranes of the oral cavity and the gastrointestinal tract. Many of these infections are caused by endogenous enteric organisms. Compared with patients have profound and prolonged neutropenia (longer than 14 days), patients with short-lived neutropenia (up to 10 days) have a lower risk of developing infections and respond better to empiric antimicrobial therapy when infection does develop. Febrile neutropenic patients were hospitalized for the administration of empiric, broad-spectrum intravenous antibiotic therapy.
Various studies have shown the efficacy of protective isolation and prophylactic oral antibiotics in preventing neutropenic infections before they were admitted for empiric antibiotics. Combinations of oral, nonabsorbable antibiotics aimed at total gastrointestinal decontamination are often poorly tolerated by patients and may encourage the acquisition of resistant organisms. The alternative approach of selective gastrointestinal decontamination aims to eliminate the aerobic flora of the gut but to preserve the anaerobic flora of the gut, and hence, the colonization resistance of the host is maintained. Co-trimoxazole is a popular drug for this purpose in the past and more recently, fluoroquinolones (e.g.ciprofloxacin, ofloxacin, and levofloxacm) have been shown to be effective. However, breakthrough gram-positive infections and the emergence of resistant gram-negative bacilli are of concern with these agents.
The therapeutic and toxic effects of anti-cancer agents such as cisplatin, anthracyclines, bleomycins, alkylating agents, various cytokines and many DNA damage and apoptosis inducing agents are thought to be mediated by reactive oxygen species (ROS), including superoxide and hydroxy radicals. The symptoms general malaise, poor appetite and signs of inflammations during chemotherapy are also part of the results of free radical damage. Dietary intake of anti-oxidant, particularly the antioxidant vitamins, vitamin C and E, beta-carotene, has been associated with a diminished risk of cancers at various anatomical sites. The thiol-containing anti-oxidant, aminofostine, and lipoate are reported to decrease the chemotherapy-induced side effects. However, theoretically it is, there is no convincing evidence of clinical applicable anti-oxidants for the treatment of chemotherapy induced toxicities.
The anti-oxidant can eliminate not only the chemotherapeutic agents induced normal tissue damage but also enhance the cytotoxicity of chemotherapeutic agents in a p53-independent induction of p21 expression in cancer cell.
The toxic effects of anti-cancer agents caused by DNA damage are thought to be mediated by reactive oxygen species, the anti-oxidant can eliminate not only the chemotherapeutic agents induced normal tissue damage, but also enhance the cytotoxicity of themotherapeutic agents in a p53-independent induction of p21 expression in cancer cells.